Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Reply to ‘F508del-CFTR is not corrected by thymosin α1’

Nature Medicine volume 24, pages 891–893 (2018)Cite this article

Subjects

Romani et al. reply: We thank Matthes et al.1 for their comment on our article that reported on the potential therapeutic activity of thymosin alpha 1 (Tα1) in cystic fibrosis (CF)2. Their reported failure to detect any increase in cystic fibrosis transmembrane conductance regulator (CFTR)-mediated current in primary human bronchial epithelial (HBE) cells from four patients and in CFBE41o- cells treated with Tα1 is a highly relevant issue, as it questions the molecule’s corrector activity that we reported in our recent paper2. Nevertheless, careful examination of their data reveals that this issue might not be due to biologic variability but rather to differences in the handling of the peptide.

Before discussing the handling issue, we first want to note that the ability of Tα1 to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO1)2, which promotes the tolerogenic pathway of tryptophan catabolism2 as well as autophagy3, may explain both the anti-inflammatory and the corrector activity of Tα1 in CF2, in accordance with a potential for autophagy in rescuing CFTR function4. IDO1 and the deubiquitinating enzyme ubiquitin-specific peptidase 36 (USP36)—whose epigenetic modifications are linked to lung function and disease5—are similarly deficient in CF2,6. Thus, the extent of the residual activity of both enzymes in individual patients likely impacts the corrector activity conferred by Tα1. Indeed, person-to-person genetic and epigenetic differences may account for biological variability in response to Tα1.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Matthes, E. et al. Nat. Med. https://doi.org/10.1038/s41591-018-0079-6 (2018).

  2. Romani, L. et al. Nat. Med. 23, 590–600 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. McGaha, T. L. Oncotarget 6, 21771–21772 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Luciani, A. et al. Nat. Cell Biol. 12, 863–875 (2010).

    Article  PubMed  CAS  Google Scholar 

  5. Lee, M. K., Hong, Y., Kim, S. Y., Kim, W. J. & London, S. J. Epigenomics 9, 971–984 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Iannitti, R. G. et al. Am. J. Respir. Crit. Care Med. 187, 609–620 (2013).

    Article  PubMed  CAS  Google Scholar 

  7. Grottesi, A. et al. Peptides 19, 1731–1738 (1998).

    Article  PubMed  CAS  Google Scholar 

  8. Mandaliti, W. et al. Amino Acids 48, 1231–1239 (2016).

    Article  PubMed  CAS  Google Scholar 

  9. Tomati, V. et al. JCI Insight 3, 98699 (2018).

    Article  PubMed  Google Scholar 

  10. Srivastava, K. R. et al. RSC Advances 7, 27981–27991 (2017).

    Article  CAS  Google Scholar 

  11. Srivastava, K. R., Kumar, A., Goyal, B. & Durani, S. J. Phys. Chem. B 115, 6700–6708 (2011).

    Article  PubMed  CAS  Google Scholar 

  12. Chioccioli M. et al. Preprint at bioRxiv https://doi.org/10.1101/223024 (2017).

Download references

Acknowledgements

We thank collaborators at the University of Perugia, Tor Vergata, University La Sapienza and Istituto Italiano di Tecnologia (IIT) for CD, light scattering, FT-IR analysis and reagent supply. This study was supported by the Specific Targeted Research Project FunMeta (ERC-2011-AdG-293714 to L.R.).

Author information

Authors and Affiliations

  1. Department of Experimental Medicine, University of Perugia, Perugia, Italy

    Luigina Romani, Claudia Stincardini, Luigi Sforna, Giorgia Renga, Marina M. Bellet, Claudio Costantini, Paolo Puccetti & Mauro Pessia

  2. Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy

    Stefano Giovagnoli

  3. Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Rome, Italy

    Maurizio Paci

  4. European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

    Valeria R. Villella & Luigi Maiuri

  5. Centre de Recherche des Cordeliers, INSERM U1138, Université Paris Descartes, Paris, France

    Guido Kroemer

  6. Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France

    Guido Kroemer

  7. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France

    Guido Kroemer

  8. Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, Sweden

    Guido Kroemer

  9. Department of Health Sciences, University of Piemonte Orientale, Novara, Italy

    Luigi Maiuri

  10. Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA

    Allan Goldstein

  11. University San Raffaele, Rome, Italy

    Enrico Garaci

Authors
  1. Luigina Romani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claudia Stincardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefano Giovagnoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maurizio Paci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valeria R. Villella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luigi Sforna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giorgia Renga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marina M. Bellet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claudio Costantini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paolo Puccetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guido Kroemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Luigi Maiuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mauro Pessia
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Allan Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Enrico Garaci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luigina Romani.

Ethics declarations

Competing interests

A patent application by L.R. and E.G. is pending (filing date, 9 February 2016; RM2015A000056 and 102015000053089, Italian Patent Office).

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Romani, L., Stincardini, C., Giovagnoli, S. et al. Reply to ‘F508del-CFTR is not corrected by thymosin α1’. Nat Med 24, 891–893 (2018). https://doi.org/10.1038/s41591-018-0080-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-018-0080-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing